Werner F. List

Remifentanil versus morphine analgesia and sedation for mechanically ventilated critically ill patients: A randomized double blind study

Background: The rapid onset and offset of action of remifentanil could make it quickly adjustable to the required level of sedation in critically ill patients. The authors hypothesized that the efficacy of a remifentanil-based regimen was greater than that of a morphine-based regimen. Methods: Forty intent-to-treat patients were randomly allocated to receive a blinded infusion of either remifentanil 0.15 &mgr;g·kg−1·min−1 or morphine 0.75 &mgr;g·kg−1·min−1. The opioid infusion was titrated, in the first intent, to achieve optimal sedation defined as Sedation Agitation scale of 4. A midazolam open-label infusion was started if additional sedation was required. Results: The mean percentage hours of optimal sedation was significantly longer in the remifentanil group (78.3 ± 6.2) than in the morphine group (66.5 ± 8.5). This was achieved with less frequent infusion rate adjustments (0.34 ± 0.25 changes/h) than in the morphine group (0.42 ± 0.22 changes/h). The mean duration of mechanical ventilation and extubation time were significantly longer in the morphine group (18.1 ± 3.4 h, 73 ± 7 min) than in the remifentanil group (14.1 ± 2.8 h, 17 ± 6 min), respectively. Remifentanil mean infusion rate was 0.13 ± 0.03 &mgr;g·kg−1·min−1, whereas morphine mean infusion rate was 0.68 ± 0.28 &mgr;g·kg−1·min−1. More subjects in the morphine group (9 of 20) than in the remifentanil group (6 of 20) required midazolam. The incidence of adverse events was low and comparable across the two treatment groups. Conclusions: A remifentanil-based regimen was more effective in the provision of optimal analgesia-sedation than a standard morphine-based regimen. The remifentanil-based regimen allowed a more rapid emergence from sedation and facilitated earlier extubation.

The effect of different stages of neuromuscular block on the bispectral index and the bispectral index-XP under remifentanil/propofol anesthesia.

Facial electromyographic activity and neuromuscular block could influence bispectral index (BIS) depth of anesthesia monitoring. In this study we examined, in 30 patients undergoing general surgical procedures, the effect of different stages of neuromuscular block on BIS monitoring and compared the conventional A-2000 BIS™ (BIS3.4) with the new BIS-XP™ (BISXP). At deep surgical anesthesia BIS3.4 of approximately 40, under a propofol 3.61 μg/mL target-controlled infusion and a 0.15–0.3 μg·kg−1·min−1 remifentanil infusion, mivacurium 0.15 mg/kg was administered. The onset of neuromuscular block triggered a brief transient odd divergence in response that manifested as a BIS3.4 increase from 43 ±4 to 49±7 (P = 0.007) and a BISXP decline from 41 ±3 to 35 ±3 (P = 0.003) at 1 ±0.2 min. Then, 2.5 ±1 min after mivacurium administration, both monitors returned to baseline values of 43 ±5 and 40 ± 4, respectively. After that, BIS3.4 and BISXP did not significantly change during complete neuromuscular block or during various levels of neuromuscular recovery. At all phases, BISXP was significantly lower than BIS3.4. Our study indicated that the BIS3.4/BISXP bias and the wide limits of agreement do not allow values given by the two monitors to be used interchangeably.

The Neuromuscular Transmission Module Versus the Relaxometer Mechanomyograph for Neuromuscular Block Monitoring

The neuromuscular transmission module (M-NMT) is an integrated piezoelectric motion sensor module incorporated in the AS/3™ anesthesia monitor. We compared the neuromuscular block of 0.6 mg/kg rocuronium (twice the 95% effective dose) monitored by the M-NMT with that monitored by the Relaxometer® mechanomyograph (MMG). The two monitors were alternately allocated to the left or right hands of 20 patients. T1%, the first twitch of the train-of-four (TOF), and the TOF ratio (T4/T1) were used for evaluating the neuromuscular block. There was no significant difference in the mean (min) ± sd onset time or time to 0.8 TOF ratio recovery measured by the M-NMT (1.5 ± 0.3, 49.4 ± 8.1) compared with MMG (1.8 ± 0.6, 50.9 ± 9.9), respectively. However, the time (min) to 25% T1 recovery was significantly longer when monitored by the M-NMT (25.6 ± 8) than by the MMG (20.2 ± 6.3). During recovery from neuromuscular block, the difference between the TOF ratios measured by the two monitors showed a bias of −0.031, and the limits of agreement (bias ±1.96 sd) were −0.281 and +0.22. The M-NMT monitor could determine the time to tracheal intubation as well as full recovery from neuromuscular block, but it lagged behind the MMG in determining the time to rocuronium repeat dose administration.

End-stage renal failure reduces central clearance and prolongs the elimination half life of remifentanil

PurposeTo evaluate the pharmacokinetics of remifentanil in 13 end-stage renal failure patients compared to matched control patients with normal renal function.MethodsRemifentanil was infused for 20 min at a rate of 0.1 μg·kg−1·min−1. Serial arterial blood samples (3 mL) were drawn at the start of infusion (zero), five, ten, 15, 20, 22.5, 25, 27.5, 30, 35, 40, 45, 50, 55 and 60 min. Blood samples were immediately preserved with citric acid and chilled on ice. High performance liquid chromatography-tandem mass spectrometry concentration assay was performed using GI 95779B internal standard.ResultsA two-compartment pharmacokinetic model provided an adequate fit for individual patient data. There was no difference in the mean ± SD distribution half life (t1/2) between the renal failure group (1.65 ± 0.7 min) and the control group (1.58 ± 0.54 min). There was a significant difference in the central clearance (Clc) and elimination half life (t1/2 ß) between the renal failure group (28 ± 7 mL·kg−1·min−1 and 18.86 ± 2.06 min, respectively) and the control group (46.3 ± 13.8 mL·kg−1·min−1 and 16.35 ± 2.99 min, respectively). Remifentanil blood concentrations were significantly higher in the renal failure group than in the control group.ConclusionWe have demonstrated a significant reduction in the Clc and a prolongation of t1/2 ß of remifentanil in end-stage renal failure patients. While statistically significant, these variations in the pharmacokinetics of remifentanil were clinically modest and may be explained by a reduced volume of distribution in the period following hemodialysis.RésuméObjectifÉvaluer la pharmacocinétique du rémifentanil chez 13 patients présentant une insuffisance rénale terminale, comparés à des témoins appariés dont la fonction rénale est normale.MéthodeLe rémifentanil a été perfusé pendant 20 min à 0,1 μg·kg−1·min−1. Une série d’échantillons de sang artériel (3 mL) a été prélevée au début de la perfusion (zéro), puis à cinq, dix, 15, 20, 22,5, 25, 27,5, 30, 35, 40, 45, 50, 55 et 60 min. Le sang a été préservé avec de l’acide citrique et conservé sur de la glace. Une analyse des concentrations par chromatographie liquide haute performance et spectrométrie de masse en tandem a été réalisée en utilisant un étalon interne GI 95779B.RésultatsUn modèle pharmacocinétique à deux compartiments a fourni un ajustement adéquat des données de chaque patient. II n’y a pas eu de différence de demi-vie de distribution moyenne ± l’écart type (t1/2 α) entre les patients atteints d’insuffisance renale (1,65 ± 0,7 min) et les patients témoins (1,58 ± 0,54 min). II y a eu une différence significative de clairance centrale (Clc) et de demi-vie d’élimination (t1/2 ß) entre le groupe d’insuffisance rénale (28 ± 7 mL·kg−1·min−1 et 18,86 ± 2,06 min, respectivement) et le groupe témoin (46,3 ± 13,8 mL·kg−1·min−1 et 16,35 ± 2,99 min, respectivement). Les concentrations sanguines de rémifentanil ont été significativement plus élevées chez les patients atteints d’insuffisance rénale.ConclusionNous avons démontré une réduction significative de la Clc et une prolongation de t1/2 ß du rémifentanil chez des patients atteints d’insuffisance rénale terminale. Quoique statistiquement significatives, ces variations de la pharmacocinétique du rémifentanil sont cliniquement faibles et peuvent s’expliquer par la réduction du volume de distribution qui suit l’hémodialyse.

Assessment of accelerography with the TOF-GUARD : a comparison with electromyography

The TOF-GUARD is a new device for monitoring the neuromuscular function using acceleration measurement. It is quick and easy to apply and does not require a rigid support for the arm. Forty-one patients were studied to assess the monitoring of vecuronium neuromuscular block (NMB) using accelerography by the TOF-GUARD compared with electromyography by the Relaxograph. Although the mean first twitch (T1%) and mean train-of-four (TOF) ratios measured by the TOF-GUARD corresponded to a certain extent with the Relaxograph, the wide variations of the values for individual patients measured by the TOF-GUARD compared with the Relaxograph and the differences in clinical duration and recovery index between the two monitors do not allow the values of the two monitors to be used interchangeably. The levels at intubation as well as at full recovery of the patients can be assessed equally by the two monitors. Thus, the TOF-GUARD is a reliable clinical monitor in daily anaesthesia practice.

Total intravenous anesthesia with remifentanil, propofol and cisatracurium in end-stage renal failure.

PurposeTo compare recovery parameters of total intravenous anesthesia (TIVA) with remifentanil and propofol, hemodynamic responses to perioperative events, and pharmacodynamic parameters of cisatracurium in 22 end-stage renal failure and 22 normal renal function patients.MethodsAnesthesia was induced with 2–3 mg·kg−1 propofol and I mg·kg−1 remifentanil and maintained with 75 μg·kg−1·min− propofol and propofol initial infusion of 0.2 μg·kg−1·min− propofol. Arterial pressure and heart rate were maintained by remifentanil infusion rate adjustments. The first twitch (TI) was maintained at 25% by an infusion of cisatracurium.ResultsThere was no difference in the time to maintenance of adequate respiration, date of birth recollection, first analgesic administration, between the renal failure (4.8 ± 2.5, 7.8 ± 3.2, 12.3 ± 5.3 min respectively) and the control group (5.2 ± 2.8, 8.1 ±3.1, 12.7 ± 5.5 min): nor were there any differences in the time to 25% TI recovery, TI recovery from 25% to 75%, or cisatracurium infusion rate between the renal failure group (32.1 ± 10.8 min, 18.2 ±5.5 min, 0.89 ± 0.29 μg·kg−1·min− respectively) and the control group (35.9 (7.9 min, 18.4 ± 3.8 min, 0.95 ± 0.22 μg·kg−1·min−).ConclusionEnd-stage renal failure does not prolong recovery from TIVA with remifentanil and propofol, or the recovery from cisatracurium neuromuscular block.RésuméObjectifComparer les paramètres de la récupération après une anesthésie exclusivement intraveineuse (AEI) avec du rémifentanil et du propofol, les réponses hémodynamiques aux circonstances périopératoires et les paramètres pharmacodynamiques du cisatracurium chez 22 patients au stade d’insuffisance rénale terminale (SIRT) et chez 22 patients sans problème rénal.MéthodeL’anesthésie a été induite avec 2–3 μg·kg−1·min− de propofol et I μg·kg−1 de rémifentanil et maintenue avec 75 μg·kg−1·min− de propofol et une perfusion initiale de 0,2 μg·kg−1·min− de propofol. La tension artérielle et la fréquence cardiaque ont été maintenues par des ajustements de la vitesse de perfusion de rémifentanil. La première stimulation musculaire (twitch T1) a été maintenue à 25 % par une perfusion de cisatracurium.RésultatsAucune différence n’a été notée, quant au temps nécessaire au maintien d’une respiration adéquate, au rappel de sa date de naissance et à l’administration d’un premier analgésique, entre les groupes SIRT (4,8 ±2,5; 7,8 ± 3,2; 12,3 ± 5,3 min respectivement) et témoin (5,2 ± 2,8; 8,1 ±3,1; 12,7 ± 5,5 min). Également, aucune différence de temps nécessaire à la récupération d’un T1 à 25 %, d’un T1 de 25 % à 75 %, ou de vitesse de perfusion du cisatracurium, entre les groupes SIRT (32,1 ± 10,8 min; 18,2 ± 5,5 min; 0,89 ± 0,29 μg·kg−1·min− respectivement) et témoin (35,9 ± 7,9 min; 18,4 ± 3,8 min; 0,95 ± 0,22 μg·kg−1·min−).ConclusionLe stade d’insuffisance rénale terminale ne prolonge pas la récupération après l’AEl avec du rémifentanil et du propofol ou la récupération après un blocage neuromusculaire avec du cisatracurium.

Geographic Regional Differences in Rocuronium Bromide Dose-Response Relation and Time Course of Action An Overlooked Factor in Determining Recommended Dosage

Background:Geographic location is not acknowledged as a stratifying factor that can directly affect drug potency, because drugs are still licensed with the same recommended dose for different geographic regions. The aim of the current study was to compare the potency and duration of action of rocuronium bromide in 54 patients in three countries with different life habits, diet, and ambient conditions, namely white Austrians, white North Americans, and Han Chinese in China. Methods:Neuromuscular block of six consecutive 50-&mgr;g/kg rocuronium incremental doses followed by 300 &mgr;g/kg was evaluated using the Relaxometer mechanomyograph (Groningen University, Groningen, Holland). Dose–response curves were created using log-dose-probit transformation. The authors compared rocuronium bromide ED50, ED90, and ED95 (effective doses required for 50%, 90%, and 95% first twitch depression, respectively) as well as Dur25 and Dur0.8 (times from last incremental dose administration until 25% first twitch and 0.8 train-of-four ratio recovery, respectively) in patients of the three countries. Results:Rocuronium ED50, ED90, and ED95 were significantly higher in Austrian patients (258 ± 68, 530 ± 159, and 598 ± 189 &mgr;g/kg) and Chinese patients (201 ± 59, 413 ± 107, and 475 ± 155 &mgr;g/kg) compared with American patients (148 ± 48, 316 ± 116, and 362 ± 149 &mgr;g/kg, respectively). Dur25 and Dur0.8 were significantly shorter in Austrian patients (22.3 ± 5.5 and 36.9 ± 12.8 min) and Chinese patients (30.4 ± 7.5 and 45.7 ± 15.9 min) compared with American patients (36.7 ± 8.5 and 56.2 ± 16.7 min, respectively). Conclusions:The authors demonstrated a significant difference in rocuronium potency and duration of action among patients in the three countries. Larger studies are required for determining dosage recommendations for different geographic regions.

Side-effects after inhalational anaesthesia for paediatric cerebral magnetic resonance imaging.

Background: The aim of this study was to evaluate the type, incidence and duration of postprocedure side‐effects in 168 children within the first 72 h after inhalational anaesthesia for magnetic resonance imaging (MRI).

Brain death and bioelectrical brain activity.

The effect of mechanical vibration and light stimulation on the ongoing and evoked bioelectrical activity was studied in two cases with clinically defined brain death and two other patients with severe head injury, one of them with an isoelectric EEG. The importance of such stimulation sequences for the definition of brain death is discussed, with particular emphasis on mechanical vibration.

A comparison of mivacurium infusion requirements between young and elderly adult patients.

Forty-one patients of ASA classes I or II, undergoing elective surgery, were divided into two groups: young, 18-41 years (mean 31), and elderly, 64-79 years (mean 71). The integrated evoked compound electromyogram of the adductor pollicis muscle elicited by stimulation of the ulnar nerve was used to monitor the neuromuscular block of the non-depolarizing muscle relaxant mivacurium. An initial dose of mivacurium 0.15 mg kg-1 allowed six excellent, nine good, three adequate and three poor intubations in the young group, and nine excellent, eight good, three adequate and no poor intubations in the elderly group. Patients recovered until 1-2 stimuli of the train-of-four were visible, and an infusion of mivacurium was started (0.5 mg kg-1 h-1). At 3 min intervals the rate was adjusted by +/- 0.05 mg kg-1 h-1 (+/- 10% initial rate), as indicated during anaesthesia which was provided by nitrous oxide in oxygen, infusion of propofol, and fentanyl supplements. In the first 30 min, the young group had their mivacurium requirement increased to 111.4% (0.56 mg kg-1 h-1), which was reached in the first 15 min, after which it gradually decreased to 92.9% (0.46 mg kg-1 h-1). The elderly groups requirements decreased from the start, to 78.5% (0.39 mg kg-1 h-1). The difference between the two groups was significant (P < 0.05). After the first 30 min, both groups requirements decreased, with time, but with no statistically significant differences.